Molloy Timothy, Wang Yao, Murrell George
Orthopaedic Research Institute, St George Hospital Campus, University of New South Wales, Sydney, Australia.
Sports Med. 2003;33(5):381-94. doi: 10.2165/00007256-200333050-00004.
Tendon healing is a complex and highly-regulated process that is initiated, sustained and eventually terminated by a large number and variety of molecules. Growth factors represent one of the most important of the molecular families involved in healing, and a considerable number of studies have been undertaken in an effort to elucidate their many functions. This review covers some of the recent investigations into the roles of five growth factors whose activities have been best characterised during tendon healing: insulin-like growth factor-I (IGF-I), transforming growth factor beta (TGFbeta), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). All five are markedly up-regulated following tendon injury and are active at multiple stages of the healing process. IGF-I has been shown to be highly expressed during the early inflammatory phase in a number of animal tendon healing models, and appears to aid in the proliferation and migration of fibroblasts and to subsequently increase collagen production. TGFbeta is also active during inflammation, and has a variety of effects including the regulation of cellular migration and proliferation, and fibronectin binding interactions. VEGF is produced at its highest levels only after the inflammatory phase, at which time it is a powerful stimulator of angiogenesis. PDGF is produced shortly after tendon damage and helps to stimulate the production of other growth factors, including IGF-I, and has roles in tissue remodelling. In vitro and in vivo studies have shown that bFGF is both a powerful stimulator of angiogenesis and a regulator of cellular migration and proliferation. This review also covers some of the most recent studies into the use of these molecules as therapeutic agents to increase the efficacy and efficiency of tendon and ligament healing. Studies into the effects of the exogenous application of TGFbeta, IGF-I, PDGF and bFGF into the wound site singly and in combination have shown promise, significantly decreasing a number of parameters used to define the functional deficit of a healing tendon. Application of IGF-I has been shown to increase in the Achilles Functional Index and the breaking energy of injured rat tendon. TGFbeta and PDGF have been shown separately to increase the breaking energy of healing tendon. Finally, application of bFGF has been shown to promote cellular proliferation and collagen synthesis in vivo.
肌腱愈合是一个复杂且高度受调控的过程，由大量各种各样的分子启动、维持并最终终止。生长因子是参与愈合的最重要分子家族之一，已经开展了大量研究以阐明其多种功能。本综述涵盖了近期对五种生长因子作用的一些研究，这些生长因子在肌腱愈合过程中的活性已得到最佳表征：胰岛素样生长因子-I（IGF-I）、转化生长因子β（TGFβ）、血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）和碱性成纤维细胞生长因子（bFGF）。这五种生长因子在肌腱损伤后均显著上调，并在愈合过程的多个阶段发挥作用。在多个动物肌腱愈合模型中，IGF-I已被证明在早期炎症阶段高表达，似乎有助于成纤维细胞的增殖和迁移，并随后增加胶原蛋白的产生。TGFβ在炎症期间也有活性，具有多种作用，包括调节细胞迁移和增殖以及纤连蛋白结合相互作用。VEGF仅在炎症期后产生水平最高，此时它是血管生成的强大刺激因子。PDGF在肌腱损伤后不久产生，有助于刺激包括IGF-I在内的其他生长因子的产生，并在组织重塑中发挥作用。体外和体内研究表明，bFGF既是血管生成的强大刺激因子，也是细胞迁移和增殖的调节因子。本综述还涵盖了近期对这些分子作为治疗剂使用以提高肌腱和韧带愈合的疗效和效率的一些研究。单独或联合将TGFβ、IGF-I、PDGF和bFGF外用于伤口部位的研究已显示出前景，显著降低了用于定义愈合肌腱功能缺陷的一些参数。IGF-I的应用已被证明可提高跟腱功能指数和受伤大鼠肌腱的断裂能量。TGFβ和PDGF已分别被证明可增加愈合肌腱的断裂能量。最后，bFGF的应用已被证明可促进体内细胞增殖和胶原蛋白合成。
